Live vector-based multivalent vaccine against cecal colonisation of Campylobacter jejuni in commercial chickens

Summary 

Campylobacter jejuni (C. jejuni) is one of the major causes of diarrhoeal diseases in humans and is highly prevalent in Low and Middle-Income counties (LMICs). Although C. jejuni has a broad host range, chickens remain the primary source of human infection. Intriguingly, C. jejuni naturally inhabits chicken’s gut with little or no sign of diseases or illness, while in the case of humans, C. jejuni causes acute gastroenteritis and several autoimmune disorders. Except for bio‐security measures, currently, no vaccine is available for humans or chickens. Moreover, with the high prevalence of antibiotic-resistant C. jejuni strains in developing countries, including India, Campylobacteriosis has become a more pressing global health issue. In search for effective measures to control C. jejuni, our group recently identified multiple vaccine targets which are generally associated with bacterial attachment to host cells and facilitate disease progression.

For this study, we modified a food-grade probiotic bacteria Lactococcus lactis (L. lactis), a commonly used bacterial strain to ferment dairy products, to express the multiple target proteins of C. jejuni. In the proposed research, we intend to use a combination of these modified recombinant bacteria (rL. lactis) as an oral vaccine against C. jejuni in commercial chickens. We expect that in addition to the general health benefits of probiotics, the combinatorial application of multiple vaccine targets will (combination of CadF, JlpA, and Hcp of C. jejuni) prevent C. jejuni colonization in vaccinated chickens, ensuring better poultry health and reduce the risk of human infection via the food chain.

 Project Outcomes

Diarrhoeal diseases are the second leading cause of preventable death, especially among children under five in developing countries, with 2-3 million deaths per year 1-4. The major bacterial diarrhoeal illness is mediated by the faecal-oral transmission of Escherichia coli, Salmonella, Shigella, Vibrio cholerae, Yersinia enterocolitica, and Campylobacter jejuni (C. jejuni). Among them, C. jejuni infection (campylobacteriosis) is considered the major bacterial cause of diarrhoeal disease in humans and is highly prevalent in Low- and Middle-Income Countries (LMICs) 4–6. Although C. jejuni has a broad host range, poultry, particularly chickens, remain the primary source of human transmission 7,8. Recently, we have demonstrated the role of major surface-expressed colonization protein (SECPs) of C. jejuni in mediating host cell adhesion, invasion, and subsequent pathogenesis in both avian and non-avian hosts 2,3. Considering our central hypothesis to reduce the number of C. jejuni in poultry intestines, we have presented here a novel mucosal immunisation strategy using a food-grade engineered live vector (such as Lactococcus lactis). Results from this study altogether advocate the current modality of oral vaccine as a safe and cost-effective approach to reduce pathogen load in the primary host (chickens). Since systemic immunisation would be time-consuming, labor-intensive, and costly, we propose that mucosal immunisation using a live vectored-based delivery platform could be a promising alternative when large numbers of flocks are needed to be immunised against C. jejuni. 

 

 

 

Amirul MallickDr Amirul Islam Mallick
Associate Professor
Indian Institute of Science Education and Research Kolkata (IISER Kolkata)
India

Collaborators:

Dr. Ozan Gundogdu, Assistant Professor, London School of Hygiene and Tropical Medicine, UK